ABSTRACT Hernia recurrence is seen in up to 60% of patients who require the use of a soft tissue prosthesis for a bridging abdominal wall repair (AWR). We hypothesize that these failures occur from one of two mechanisms: 1) current alloplastic and biologically derived soft tissue prostheses fail mechanically at the tissue-prosthesis interface due to high initial stiffness and 2) chronic failure over time due to attenuation and loss of structural integrity of the biologic prosthesis. All current alloplastic and biologic prostheses are optimized for mechanical strength and are much stiffer than the native abdominal wall. The abrupt transition at the interface between the stiff prosthesis and the more compliant abdominal wall predisposes to acute mechanical failure. Furthermore, the acellular, biologic materials currently used for bridging repairs are inadequate because, even if the acute repair holds, the materials invariably degrade and attenuate with time. To date, there are no biologic materials that allow for sufficient cellular ingrowth to prevent this eventual matrix degradation. To address these two failure mechanisms specifically, our lab has fabricated a cellular neo-tendinous (CNT) tissue-engineered construct that has properties designed to eliminate the mechanical mismatch of the interface with the native abdominal wall while having robust cellularity to incorporate into the abdominal wall, regenerate native tissue in the defect area and to maintain structural integrity over time. Previous studies using this construct fabrication technology as a graft in an ACL reconstruction model have shown marked improvement of biomechanical properties after several months in vivo. Preliminary data using the CNTs show our ability to customize the stiffness of these constructs in vitro and have demonstrated biointegration after implantation at an acute time point. This approach differs from dogma and from most current work in this area; instead of focusing on structural patches, we seek to develop a way to enact a living, adaptable, self-maintaining abdominal wall repair. In this study, we will evaluate the short and long-term efficacy, incorporation, and regenerative capacity of CNTs as tissue prosthesis for abdominal wall repair comparing compliant versus stiff constructs and evaluating the role of living cells in these outcome measures. Our ultimate goal is to improve the care of patients with ventral hernias and other abdominal wall defects.